miRNA-135b up-regulates the methylation of APC gene in the occurrence and development of type 2 diabetes mellitus / 中华内分泌外科杂志

ABSTRACT

Objective:To investigate the relationship between the DNA methylation of APC gene and the occurrence and development of diabetic nephropathy (DN) in peripheral blood, and to analyze its effect on gene transcription and protein expression levels.Methods:From Mar. 2018 to Mar. 2020, 96 patients with DN and 100 healthy examinees in Department of Nephrology, Hangzhou First people’s Hospital Affiliated to Zhejiang University were selected as the research objects, and the methylation level, mRNA level and protein expression level of CpG island of APC gene in the two groups were detected.Results:The methylation level of APC-1 island in DN patients was 3.05%±0.65%, which was significantly higher than that in healthy controls 2.34%±0.56% ( t=5.231, P<0.001) ; The methylation level of APC-2 island was 1.65%±0.37%, which was significantly higher than that of the healthy control group 1.17%±0.29% ( t=4.381, P<0.001) ; Pearson correlation analysis showed that the methylation level of APC-1 island was significantly positively correlated with the ration of serum creatinine and uric acid (all P<0.05) , and the methylation level of APC-2 island was significantly positively correlated with uric acid ( P<0.05 ) ; The methylation level of APC-1 island in DN patients was negatively correlated with the relative expression of mRNA ( r=-0.426, P=0.019) and the level of APC protein ( r=-0.569, P=0.004) . The expression of miRNA-135b in rats in the overexpression lentivirus group was significantly higher than that in the no-virus group ( t=5.432, P<0.001) and DN group ( t=5.812, P<0.001) ; The APC methylation level of rats in the miRNA-135b overexpression lentivirus group was also significantly higher than that in DN group ( t=6.217, P<0.001) and the rats in the no-virus group ( t=6.446, P<0.001) . Conclusion:miRNA-135b may participate in the occurrence and development of DN by up-regulating DNA methylation of APC gene and reducing mRNA and protein expression levels.